Purpose: A physiologic sagittal alignment of the cervical spine, including the ability to maintain level gaze, is essential to maintaining functionality during activities of daily living. Consequenty, cervical sagittal malalignment has been linked to disability and poor health-related quality of lif scores due to disabling symptoms of neck pain and neurological deficit. The goal of this study is to establish the link between radiographic or clinical measures of sagittal malalignment and objective measures of cervical pathomechanics. Hypotheses: The long-term goal of our research is to understand the mechanisms responsible for cervical malalignment-related symptoms of neck pain, muscle fatigue, and neurological deficit so as to improve treatment rationale. Our central hypothesis is that in the presence of cervical sagittal malalignment, the compensatory realignment of cervical segments that is necessary in order to maintain horizontal gaze will: (1) increase force demands on posterior muscles to maintain the head-neck posture in equilibrium and cause increased loading of disc & facet joints; and (2) adversely affect the foraminal and canal spaces. The hypothesis is based on our preliminary studies using a novel laboratory model of cervical sagittal imbalance that allows assessment of the effects of the independent variables on cervical spine postural and kinetic responses. Specific Aims: (1) For each combination of the independent variables of sagittal malalignment, measure the compensatory angular and translational repositioning of each cervical vertebra such that horizontal gaze is maintained, and the forces and moments that are needed to maintain the head-neck posture in equilibrium. (2) Analyze the effects of experimentally simulated sagittal malalignments on foraminal and canal spaces using CT-based specimen-specific models and kinematic data collected in Aim 1. (3) Analyze effects of simulated sagittal malalignments on stresses in bony and soft tissues of the cervical spine using CT-based specimen- specific finite element models (FEM), and the kinematic and kinetic boundary conditions quantified in Aim 1. Research Plan: We will use a combination of (1) experimental studies on human cadaveric cervical spine specimens, (2) CT-based specimen-specific kinematic models, and (3) CT-based specimen-specific finite element models, to achieve our goals. Experiments on 55 fresh human cadaveric cervical spine specimens (occiput-T1) will simulate a variety of clinically relevant sagittal malalignments. Experimentally measured quantities, namely, compensatory vertebral motions, and kinematic and kinetic boundary conditions at the ends of the specimen, will serve as inputs to the specimen-specific kinematic and FE models to assess the effects of each sagittal malalignment on canal & foramen dimensions and facet loading. The three study- components together will define cervical spine mechanics in terms of the following outcome variables: Kinetic: loading of muscles and stresses in facets & discs, with implications to muscle fatigue, disc & facet degeneration, and neck pain; and Geometric: foraminal and canal spaces, with implications to neurologic deterioration. Statistical Analysis: Each of the 55 specimens will be tested for different combinations of the four independent variables that define sagittal malalignment, giving adequate (>80%) power for assessing the effects of the main variables and their interactions. Discrete values of the outcome variables for the intact spine and also for the different cases of simulated fusions will be analyzed using the repeated measures ANOVA. Multivariate regression analyses will be performed to assess the relative importance of independent variables in influencing the outcome and arrive at predictive equations relating dependent & independent variables. Significance: The results of this study will provide a rational basis for bringing objectivity to the present day subjective paradigms for treatment of cervical imbalance. Results will be of immediate benefit to all health care team-members who manage patients with neck pain, whether conservatively (physicians, physical therapists, chiropractors), or those who perform invasive interventions (surgeons).